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首页> 外文期刊>Neoplasia: an international journal for oncology research >Platelet-Synthesized Testosterone in Men with Prostate Cancer Induces Androgen Receptor Signaling
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Platelet-Synthesized Testosterone in Men with Prostate Cancer Induces Androgen Receptor Signaling

机译：具有前列腺癌的男性的血小板合成睾酮诱导雄激素受体信号传导

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Platelets have been long postulated to play a critical role in the pathogenesis of prostate cancer, although relatively little is known regarding the precise mechanisms involved. Androgen deprivation therapy (ADT) for prostate cancer eventually fails with relapse occurring in the form of castration-resistant prostate cancer (CRPC). CRPC tumors typically overexpress androgen receptor (AR), demonstrating continued dependence upon AR signaling. Platelets have been previously demonstrated to contain androgens, and we sought to explore the contribution of platelet-derived androgens in CRPC. In this study, we examined the role of platelet-derived androgens in vitro using platelets from men with CRPC, men with high-risk prostate cancer, and healthy male donors. A series of in vitro assays was performed to elucidate the impact of platelet-derived androgens on androgen-sensitive prostate tumor cells. By examining platelet-derived androgen effects on AR signaling in prostate tumor cells, we found that platelets, from men with CRPC and on ADT, strongly induce AR target genes and tumor cell proliferation. Moreover, we show a fully intact testosterone (T) biosynthetic pathway within platelets from its precursor cholesterol and demonstrate that platelets of CRPC patients with ADT resistance are able to generate T. Overall, our findings reveal an unknown capacity of platelets to synthesize T at functionally relevant levels in patients with lethal prostate cancer. Importantly, it suggests a novel paracrine mechanism of T production that may act to sustain CRPC state and potentiate therapeutic resistance.
机译：血小板已经长期假设在前列腺癌的发病机制中发挥着关键作用，尽管关于所涉及的精确机制，但相对较少。前列腺癌的雄激素剥夺治疗（ADT）最终因抗阉割前列腺癌（CRPC）的形式发生复发。 CRPC肿瘤通常过表达雄激素受体（AR），证明继续依赖AR信号传导。先前已经证明了血小板含有雄激素，我们试图探索CRPC中血小板衍生的雄激素的贡献。在这项研究中，我们检查了体外血小板衍生的雄激素的作用，使用具有CRPC的男性的血小板，具有高风险前列腺癌的男性和健康的男性捐赠者。进行一系列体外测定以阐明血小板衍生的雄激素对雄激素敏感前列腺肿瘤细胞的影响。通过检查前列腺肿瘤细胞中AR信号传导的血小板衍生的雄激素效应，我们发现从具有CRPC和ADT的男性，强烈诱导AR靶基因和肿瘤细胞增殖的血小板。此外，我们在血小板中显示出完全完整的睾酮（t）生物合成途径，其前体胆固醇，并证明了CRPC患者的ADT抗性的血小板能够产生T.总体而言，我们的研究结果揭示了在功能上合成了血小板的未知容量致命前列腺癌患者的相关水平。重要的是，它提出了一种新的帕拉卡碱机制，可以采取行动，以维持CRPC状态和增强治疗性。

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